Phenotyping the demographic and behavioral correlates of start hesitation in Parkinson's disease

Introduction: Freezing of gait (FOG) is a significant symptom in Parkinson's Disease (PD) that has been associated with attentional set shifting deficits, suggesting an underlying frontostriatal neurobiology. Whilst to date Start Hesitation (SH) has been regarded as a subtype of FOG, whether it shares the same underlying neural correlates remains unknown. The specific correlation of SH with other clinical features might help to elucidate its neurobiological underpinnings, which could potentially offer novel treatment strategies. Methods: In this study, 72 PD patients underwent a previously validated VR gait paradigm in either On, Off or both medication states to identify episodes of SH. Participants also underwent a standardized clinical battery covering motor and non-motor features, including neuropsychometric testing across domains of attention, language, working memory, and visuospatial function. Results: The presence of SH was identified in 48 of the 72 patients. Compared to patients without SH, those demonstrating SH had a significantly higher depression score (3.8 vs 2.2, p = 0.045) and reported more REM Sleep Behavior Disorder (5.8 vs 3.3, p = 0.005). Notably, there were no significant group differences in age, disease duration, MDS-UPDRS scores, motor phenotype, falls risk, or any cognitive domains. In those patients with SH, there were no correlations of large magnitude between the duration of SH episodes and any relevant clinical, demographic or neuropsychometric measures. Conclusion: These results suggest that the neurobiological underpinnings of SH are distinct from those reported across FOG and may relate more to brainstem pathology. Further neuroimaging and neurophysiological approaches are now required.